This invention concerns the retinoblastoma gene and methods for detecting and treating patients afflicted with a defective retinoblastoma gene.
Retinoblastoma is a neoplastic condition of the retinal cells, observed almost exclusively in children between the ages of 0 and 4 years. It affects between 1 in 34,000 and 1 in 15,000 live births in the United States. (L. E. Zimmerman, 1985, Retinoblastoma and retinocytoma, In W. H. Spencer (ed.), Ophthalmic Pathology: an Atlas and Textbook, Vol. II, Philadelphia: W. B. Saunders Co., pp. 1292–1351.) If untreated, the malignant neoplastic retinal cells in the intraocular tumor travel to other parts of the body, forming foci of uncontrolled growth which are always fatal. The current treatment for a retinoblastoma is enucleation of the affected eye if the intraocular tumor is large; for small intraocular tumors, radiation therapy, laser therapy, or cryotherapy is preferred. There is no known successful treatment for metastatic retinoblastoma. As with most cancers, morbidity and mortality are reduced if diagnosis can be made early in the course of the disease.
In 30–40% of cases of retinoblastoma, the affected individual carries a heritable predisposition to retinoblastoma and can transmit this predisposition to his or her offspring as a dominant trait (A. G. Knudson, 1971, Mutation and cancer: Statistical study of retinoblastoma, Proc. Natl. Acad. Sci., Vol. 68, pp. 820–23). Carriers of this retinoblastoma-predisposing trait are at a greatly elevated risk for development of several other forms of primary cancer, notably osteosarcoma and soft-tissue sarcoma.
The genetic locus associated with familial retinoblastoma has been assigned to the q14 band of human chromosome 13 (R. S. Sparkes et al., 1980, Science, Vol. 208, pp. 1042–44). Most retinoblastomas arise from cells which have lost both normal, dominant, homologous alleles at this retinoblastoma locus. However, individuals carrying one defective allele may be predisposed to the disease. Children who have had one eye affected by retinoblastoma or who are related to someone with retinoblastoma may be genetically predisposed and therefore at risk of developing the disease. These individuals routinely are tested for retinoblastoma every 2–3 months by an ocular examination procedure which requires placing the child under general anesthesia.